PB2307: A MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY OF ROMIPLOSTIM PLUS DEXAMETHASONE VS DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED PRIMARY IMMUNE THROMBOCYTOPENIA
Authors: M. E. Mingot Castellano, C. A. Bradbury, C. Rosso Fernández, I. Thomas, M. T. Alvarez-Román, M. Canaro, I. S. Caparrós Miranda, M. Cappechi, M. Carpenedo, G. Evans, J. T. González-Lopéz, J. R. González-Porras, I. Jarque Ramos, M. L. Lozano-Almela, M. F. Lopez Fernandez, G. Lowe, H. Lyall, C. Pascual Izquierdo, S. Pavord, R. Rayment, P. Roberts, P. Rosique Cortina, B. Sánchez-González, C. Santoro, K. Talks, D. Valcarcel-Ferreiras, F. Zaja
Journal: HemaSphere (2022)

Background: High dose glucocorticoids are recommended as initial treatment for adults with Immune primary thrombocytopenia (ITP). In the majority of patients (85%), dexamethasone is effective at increasing platelet counts, but within 6 months 50% will relapse. Romiplostim is a peptibody designed to activate the TPO receptor, leading to platelet responses in 79-95% of ITP patients as second line treatment. There is accumulating evidence that the combination of immunosuppressive drugs and TPO analogues (TPOa) may improve ITP responses. Aims: Primary objective To evaluate the superiority of romiplostim plus dexamethasone vs dexamethasone alone in patients with newly primary immune thrombocytopenia (ITP) in terms of sustained response off any ITP treatment and without WHO grade 2 or more bleeding Secondary objectives • To compare the efficacy of dexamethasone plus romiplostim vs dexamethasone in terms of complete response (CR), response (R), global response (GR), SR at 6 and 12 months and other efficacy-related endpoints • Safety and tolerability • Quality of life • Cost-effectiveness analysis comparing dexamethasone plus romiplostim vs dexamethasone (Health-resource utilization, HRU) Methods: This is an open label, randomized (1:1), phase 3 study designed to compare romiplostim plus dexamethasone vs dexamethasone alone (See figure 1). 126 patients will be enrolled in 30 study sites from Spain, United Kingdom and Italy. • Arm 1 (Romiplostim plus dexamethasone): dexamethasone 40 mg daily for 4 days only in the first cycle and subcutaneous romiplostim weekly for up to 12 months (ROM + DEX arm). Romiplostim will be tapered when platelets are ≥ 50x109/L for more than 4 weeks (see figure 2). • Arm 2 (Dexamethasone): dexamethasone 40 mg daily for 4 days for up to 3 cycles every 14 to 28 days (DEX arm). Results: Patients will be followed for a minimum of 12 months from randomization and a minimum of 6 months after discontinuing treatment with either romiplostim or dexamethasone. The following assessments will be done in these visits: platelets count, bleeding score (ITP-BAT, WHO criteria), number and characteristics of bleeds, adverse events (CTCAE version 4.03), study medication, rescue medication and concomitant medication, HRU associated with the ITP or its treatment and loss of productivity and quality of life (EQ-5D, 36-Item Short-Form Health Survey (SF-36) version 2, Investigating Choice Experiments Capability Measure–Adults (ICECAP-A) questionnaire, version 2; fatigue as measured on the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) scale, version 4). Intravenous immunoglobulins (IVIg), platelet transfusion or prednisone will be considered rescue treatment. Treatment failure definitions: • In the ROM + DEX arm, treatment failure is defined as a platelet count <30x109/L after 4 weeks of romiplostim at 10 mcg/kg/week or if rescue medication is needed to get this level of platelets despite romiplostim 10mcg/kg/week for 4 weeks. • In DEX arm, treatment failure is defined as a platelet count <30x109/L after 3 cycles of dexamethasone or if rescue medication is needed to get this level of platelets despite the 3 cycles of dexamethasone. Image:Summary/Conclusion: This study will evaluate dexamethasone and romiplostim combination in comparison to dexamethasone alone for first line ITP treatment in terms of response, sustained response off any ITP treatment (SROT), bleeding, adverse events, need for rescue treatments and quality of life.